Abstract
SummaryProton-dependent oligopeptide transporters (POTs) are important for uptake of dietary di- and tripeptides in many organisms, and in humans are also involved in drug absorption. These transporters accept a wide range of substrates, but the structural basis for how different peptide side chains are accommodated has so far remained obscure. Twenty-eight peptides were screened for binding to PepTSt from Streptococcus thermophilus, and structures were determined of PepTSt in complex with four physicochemically diverse dipeptides, which bind with millimolar affinity: Ala-Leu, Phe-Ala, Ala-Gln, and Asp-Glu. The structures show that PepTSt can adapt to different peptide side chains through movement of binding site residues and water molecules, and that a good fit can be further aided by adjustment of the position of the peptide itself. Finally, structures were also determined in complex with adventitiously bound HEPES, polyethylene glycol, and phosphate molecules, which further underline the adaptability of the binding site.
Highlights
Proton-dependent oligopeptide transporters (POTs; known by the acronyms PepTs and PTRs) are ubiquitous in bacteria and eukaryotes where they play an important role in nitrogen acquisition through proton-coupled uptake of di- and tripeptides (Daniel et al, 2006; Smith et al, 2013)
Proton-dependent oligopeptide transporters (POTs) are important for uptake of dietary di- and tripeptides in many organisms, and in humans are involved in drug absorption
Twenty-eight peptides were screened for binding to PepTSt from Streptococcus thermophilus, and structures were determined of PepTSt in complex with four physicochemically diverse dipeptides, which bind with millimolar affinity: Ala-Leu, Phe-Ala, Ala-Gln, and Asp-Glu
Summary
Quistgaard, Ali Flayhan, Joanna Pieprzyk, Christian Low. Proton-dependent oligopeptide transporters (POTs) are highly multispecific, accepting a broad range of substrates. Martinez Molledo et al characterize the substrate specificity of the POT transporter, PepTSt. Here, Martinez Molledo et al characterize the substrate specificity of the POT transporter, PepTSt They present several structures of this protein in complex with different dipeptides and other ligands, revealing that multispecificity is achieved by several complementary strategies. Martinez Molledo et al, 2018, Structure 26, 467–476 March 6, 2018 a 2018 The Author(s). Multispecific Substrate Recognition in a Proton-Dependent Oligopeptide Transporter
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